High 24-hour Level of Serum Growth Hormone in Juvenile Diabetics

Studies in five male patients with recently diagnosed juvenile diabetes showed a raised mean level of serum growth hormone, which fluctuated considerably over a 24-hour period. It is suggested that the secretion rate of growth hormone is raised in this condition.     

Biochemical and histologic presentations of female wistar rats administered with different doses of paracetamol/methionine

This study was carried out to compare the hepatoprotective effect of methionine on paracetamol treated rats at both the peaks of toxicity and absorption. Female Wistar rats were divided into 17 groups consisting of eight rats per group and treated with different doses of paracetamol/methionine (5:1). Each control rat received 5 ml of physiologic saline. The study was terminated at two different end points -the 4th and 16th hours. Results show that rats administered with toxic doses (1000 mg/kg, 3000 mg/kg, 5000 mg/kg BW) of paracetamol exhibited significant increases in the levels of ALT, AST, γ- GT compared with controls. These increases were much higher at the 16th than 4th hour but serum total protein, albumin and globulin were significantly decreased by the end of the 16th hour. Histology results of rats in the 3000 and 5000 mg/kg (by the end of the 16th hour) confirmed hepatic damage, light microscopic evaluation of liver showed remarkable centrilobular necrosis. Moreover, the presence of mononuclear cells in liver section of rats intoxicated with APAP (5000 mg/kg) suggests a possible involvement of inflammatory process which resulted in regurgitation of bilirubin leading to its elevated level as well as increase activity of ALP. The hepatoprotective effect of methionine, on the other hand, was demonstrated in these rats at the 4th and 16th hours, and both results were comparable and therefore not significantly different but elevation in GGT level still persisted. In conclusion, data obtained from this study suggest that these agents may be capable of inducing GGT, although further study is required to establish a possible relationship between methionine and this enzyme in some other animal species.     

Disparities in survival of stomach cancer among different socioeconomic groups in North-East Netherlands

Background: Survival differences in stomach cancer are depended on patient, tumour and treatment factors. Some populations are more prone to develop stomach cancer, such as people with low socioeconomic status (SES). The aim of this population based study was to assess whether differences in socioeconomic status (SES) alone, after adjusting for confounding factors, also influence survival. Methods: From 1989 to 2007 all patients with stomach cancer were selected from the cancer registry of the Comprehensive Cancer Centre North-East. Postal code at diagnosis was used to determine SES, dividing patients in three groups; low, intermediate and high SES. Associations between age, localization, grade, stage, and treatment were determined using Chi-square analysis. Relative survival analysis was used to estimate relative excess risk (RER) of dying according to SES. Results: In low SES neighbourhoods diagnosis was established at older age. More distal tumours were detected in patients with low SES, whereas pathology showed more poorly differentiated tumours in patients with high SES. Overall, more resections were performed in, and more chemotherapy was administrated to patients in high SES neighbourhoods. After adjusting for confounding factors, the risk of dying was lower for patients with high SES (RER 0.89, 95% Confidence Interval 0.81–0.98) compared to patients with low SES. Conclusion: SES proved to be an independent prognostic factor for survival in patients with stomach cancer.     

Origin and evolution of TRIM proteins: new insights from the complete TRIM repertoire of zebrafish and pufferfish

Tripartite motif proteins (TRIM) constitute a large family of proteins containing a RING-Bbox-Coiled Coil motif followed by different C-terminal domains. Involved in ubiquitination, TRIM proteins participate in many cellular processes including antiviral immunity. The TRIM family is ancient and has been greatly diversified in vertebrates and especially in fish. We analyzed the complete sets of trim genes of the large zebrafish genome and of the compact pufferfish genome. Both contain three large multigene subsets--adding the hsl5/trim35-like genes (hltr) to the ftr and the btr that we previously described--all containing a B30.2 domain that evolved under positive selection. These subsets are conserved among teleosts. By contrast, most human trim genes of the other classes have only one or two orthologues in fish. Loss or gain of C-terminal exons generated proteins with different domain organizations; either by the deletion of the ancestral domain or, remarkably, by the acquisition of a new C-terminal domain. Our survey of fish trim genes in fish identifies subsets with different evolutionary dynamics. trims encoding RBCC-B30.2 proteins show the same evolutionary trends in fish and tetrapods: they evolve fast, often under positive selection, and they duplicate to create multigenic families. We could identify new combinations of domains, which epitomize how new trim classes appear by domain insertion or exon shuffling. Notably, we found that a cyclophilin-A domain replaces the B30.2 domain of a zebrafish fintrim gene, as reported in the macaque and owl monkey antiretroviral TRIM5α. Finally, trim genes encoding RBCC-B30.2 proteins are preferentially located in the vicinity of MHC or MHC gene paralogues, which suggests that such trim genes may have been part of the ancestral MHC.     

Abiotic Racemization Kinetics of Amino Acids in Marine Sediments

The ratios of d- versus l-amino acids can be used to infer the sources and composition of sedimentary organic matter. Such inferences, however, rely on knowing the rates at which amino acids in sedimentary organic matter racemize abiotically between the d- and the l-forms. Based on a heating experiment, we report kinetic parameters for racemization of aspartic acid, glutamic acid, serine, and alanine in bulk sediment from Aarhus Bay, Denmark, taken from the surface, 30 cm, and 340 cm depth below seafloor. Extrapolation to a typical cold deep sea sediment temperature of 3°C suggests racemization rate constants of 0.50×10⁻⁵–11×10⁻⁵ yr⁻¹. These results can be used in conjunction with measurements of sediment age to predict the ratio of d:l amino acids due solely to abiotic racemization of the source material, deviations from which can indicate the abundance and turnover of active microbial populations.     

Single-cell paired-end genome sequencing reveals structural variation per cell cycle

The nature and pace of genome mutation is largely unknown. Because standard methods sequence DNA from populations of cells, the genetic composition of individual cells is lost, de novo mutations in cells are concealed within the bulk signal and per cell cycle mutation rates and mechanisms remain elusive. Although single-cell genome analyses could resolve these problems, such analyses are error-prone because of whole-genome amplification (WGA) artefacts and are limited in the types of DNA mutation that can be discerned. We developed methods for paired-end sequence analysis of single-cell WGA products that enable (i) detecting multiple classes of DNA mutation, (ii) distinguishing DNA copy number changes from allelic WGA-amplification artefacts by the discovery of matching aberrantly mapping read pairs among the surfeit of paired-end WGA and mapping artefacts and (iii) delineating the break points and architecture of structural variants. By applying the methods, we capture DNA copy number changes acquired over one cell cycle in breast cancer cells and in blastomeres derived from a human zygote after in vitro fertilization. Furthermore, we were able to discover and fine-map a heritable inter-chromosomal rearrangement t(1;16)(p36;p12) by sequencing a single blastomere. The methods will expedite applications in basic genome research and provide a stepping stone to novel approaches for clinical genetic diagnosis.     

A Secretory Golgi Bypass Route to the Apical Surface Domain of Epithelial MDCK Cells

Proteins leave the endoplasmic reticulum (ER) for the plasma membrane via the classical secretory pathway, but routes bypassing the Golgi apparatus have also been observed. Apical and basolateral protein secretion in epithelial Madin-Darby canine kidney (MDCK) cells display differential sensitivity to Brefeldin A (BFA), where low concentrations retard apical transport, while basolateral transport still proceeds through intact Golgi cisternae . We now describe that BFA-mediated retardation of glycoprotein and proteoglycan transport through the Golgi apparatus induces surface transport of molecules lacking Golgi modifications, possessing those acquired in the ER. Low concentrations of BFA induces apical Golgi bypass, while higher concentrations were required to induce basolateral Golgi bypass. Addition of the KDEL ER-retrieval sequence to model protein cores allowed observation of apical Golgi bypass in untreated MDCK cells. Basolateral Golgi bypass was only observed after the addition of BFA or upon cholesterol depletion. Thus, in MDCK cells, an apical Golgi bypass route can transport cargo from pre-Golgi organelles in untreated cells, while the basolateral bypass route is inducible.     

Modulating effect of dopamine on amplitude of GABA-produced chemocontrolled currents in multipolar spinal cord neurons of ammocaete

By using the patch-clamp method in the whole cell configuration, modulating effect of dopamine on GABA-activated currents has been studied on isolated multipolar spinal cord neurons of the ammocaete (larva of the lamprey Lampetra planeri). At application of dopamine (5 μM), there was observed in some cases a decrease of the GABA-activated current, on average, by 33.3 ± 8.7% (n = 8, p < 0.01), in other cases—an increase of the amplitude, on average, by 37.3 ± 11.8% (n = 5, p < 0.01). Concentration of GABA amounted to 2 mM. Study of action of agonists of D1- and D2-receptors on amplitude of chemocontrolled currents has shown that agonist of D1-receptors (+)-SKF-38393 (5 μM) decreases the GABA-activated current amplitude, on average, by 63.1 ± 11.7% (n = 8, p s< 0.01); the agonist of D2-receptors (−)-quinpirole (5 μM) produces in various cells the dopamine-like effects: an increase of the GABA-activated current amplitude, on average, by 61.0 ± 13.8% (n = 8, p < 0.01) and a decrease of amplitude, on average, by 55.7 ± 2.0% (n = 6, p < 0.01). It has been shown that antagonist of D2-receptors sulpiride (5 μM) does not block effects produced by dopamine. The dopamine effects were partially blocked by antagonist of D1-receptors (+)-SCH-23390 (5 μM): a decrease of the GABA-activated amplitude current amounted, on average, to 11.7 ± 1.8% (n = 7, p < 0.01), while an increase of amplitude—8.3 ± 2.0% (n = 5, p < 0.01). At the same time, effects of agonist of D1-receptors quinpirole (5 μM) were partially blocked by antagonist of D1-receptors (+)-SCH-23390: a decrease of the GABA-activated current amplitude amounted, on average, to 9.2 ± 3.4% (n = 6, p < 0.01) and an increase of amplitude—6.3 ± 1.8% (n = 10, p < 0.01). The obtained data indicate differences of mechanisms of the receptor-mediated effect of agonists of dopamine receptors on GABA-activated and potential-activated currents of multipolar neurons of the ammocaete spinal cord.     

CXCL8 Chemokines in Teleost Fish: Two Lineages with Distinct Expression Profiles during Early Phases of Inflammation

Background

During the inflammatory process, chemokine CXCL8 plays a pivotal role in recruitment of human neutrophilic granulocytes. A diversity of sequences similar to CXCL8 was reported in fish, but their evolutionary relationships and functional homology with their human homolog remain unclear.

Principal Findings

We screened fish genomes to seek for sequences related to CXCL8. A first lineage was retrieved in all teleosts, while a second CXCL8 lineage was found in zebrafish and carp only. An early inflammatory function for both lineages was indicated by several lines of evidence. The induction of carp CXCL8s, CXCb, and CXC receptor-1 and -2 was analyzed after in vitro stimulation of leukocyte subpopulations and in two in vivo inflammation models. Recombinant proteins of carp CXCL8 proteins were produced and showed significant chemotactic activity for carp leukocytes.

Conclusions

While both carp CXCL8s appear to be functional homologs of mammalian CXCL8, their different induction requirements and kinetics evoke a gene-specific sub-functionalization.